Process and intermediate compounds for the preparation of pesticidal fluoroolefin compounds

ABSTRACT

A process and intermediate compounds for the preparation of fluoroolefin compounds which are useful as pesticidal agents.

This is a divisional of application(s) Ser. No. 08/865,782 filed on May29, 1997 now U.S. Pat. No. 5,892,131 the entire disclosure of which ishereby incorporated by reference. This application claims the benefit ofdomestic priority under 35 Asc 119(e) 60/019,117, Jun. 3, 1996.

BACKGROUND OF THE INVENTION

Fluoroolefin compounds which are useful as pesticidal agents aredescribed in WO 94/06741 and GB 2,288,803-A. Those references alsodescribe processes for the preparation of fluoroolefin compounds.However, those processes are not entirely satisfactory because thefluoroolefin compounds are produced in relatively low yields. Thosereferences also fail to teach how to make the intermediate compounds ofthe present invention.

SUMMARY OF THE INVENTION

The present invention provides an effective and efficient process forthe preparation of a pesticidal fluoroolefin compound having thestructural formula I

wherein

R is hydrogen or C₁-C₄alkyl, and

R₁ is C₁-C₄alkyl or cyclopropyl, or R and R₁, are taken together withthe carbon atom to which they are attached to form a cyclopropyl group;

Ar is phenyl optionally substituted with any combination of from one tothree halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy or C₁-C₄haloalkoxy groups, or

1- or 2-naphthyl optionally substituted with any combination of from oneto three halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C_(1-C) ₄alkoxy orC₁-C₄haloalkoxy groups;

Ar₁ is phenoxyphenyl optionally substituted with any combination of fromone to five halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups,

biphenyl optionally substituted with any combination of from one to fivehalogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁C₄alkoxy or C₁-C₄haloalkoxygroups,

benzylphenyl optionally substituted with any combination of from one tofive halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy or C₁-C₄haloalkoxygroups, or

benzoylphenyl optionally substituted with any combination of from one tofive halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy or C₁-C₄haloalkoxygroups; and

the configuration of the groups ArCRR₁- and -CH₂Ar₁about

the double bond is predominately mutually trans, which process comprisesreacting a 4-aryl-2-fluoro-2-butene-1-ol compound having the structuralformula II

wherein Ar, R and R₁ are as described above, with a brominating agent toform a 4-aryl-1-bromo-2-fluoro-2-butene compound having the structuralformula III

wherein Ar, R and R₁ are as described above, and reacting the formulaIII compound with a palladium catalyst, a base, and a boronic acidhaving the structural formula IV, a boronic anhydride having thestructural formula V or a borate ester having the structural formula VI

(HO)₂B—Ar₁   (IV)  (R₂O)₂B—Ar₁   (VI)

wherein R₂ is C₁-C₄alkyl and Ar₁ is as described above.

The present invention also relates to the intermediate4-aryl-1-bromo-2-fluoro-2-butene compounds of formula III.

It is, therefore, an object of the present invention to provide aneffective and efficient process for the preparation of pesticidalfluoroolefin compounds.

It is also an object of the present invention to provide intermediatecompounds which are useful for the preparation of pesticidalfluoroolefin compounds.

Other objects and advantages of the present invention will be apparentto those skilled in the art from the description below and the appendedclaims.

DETAILED DESCRIPTION OF THE INVENTION

A preferred embodiment of the present invention comprises reacting a4-aryl-2-fluoro-2-butene-1-ol of formula II with at least about onemolar equivalent of a brominating agent, preferably in a temperaturerange of about 50° C. to 130° C., in the presence of a first solvent toform a 4-aryl-1-bromo-2-fluoro-2-butene of formula III, and reacting theformula III compound with about 0.001 to 0.1, preferably about 0.005 to0.1, molar equivalent of a palladium catalyst, at least about 2 molarequivalents, preferably about 2-6 molar equivalents of a base, and aboronic acid of formula IV, preferably 1 molar equivalent of a boronicacid in a temperature range of about 50° C. to 130° C., in the presenceof a second solvent.

The present invention also relates to the4-aryl-1-bromo-2-fluoro-2-butene compounds which are utilized in theprocess of this invention. The 4-aryl-1-bromo-2-fluoro-2-butenecompounds have the structural formula III

wherein

R is hydrogen or C₁-C₄alkyl, and

R₁ is C₁-C₄alkyl or cyclopropyl, or R and R₁ are taken together with thecarbon atom to which they are attached to form a cyclopropyl group;

Ar is phenyl optionally substituted with any combination of from one tothree halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups, or

1- or 2-naphthyl optionally substituted with any combination of from oneto three halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups; and

the configuration of the groups ArCRR₁- and -CH₂Br about the double bondis predominately mutually trans.

Exemplary of halogen hereinabove are fluorine, chlorine, bromine andiodine. The terms “C₁-C₄haloalkyl” and “C₁-C₄haloalkoxy” are defined asa C₁ -C₄alkyl group and a C₁-C₄alkoxy group substituted with one or morehalogen atoms, respectively.

The product formula I compounds may be isolated by diluting the reactionmixture with water and extracting the product with a suitable extractionsolvent. In the isolation procedure, conventional extraction solventssuch as ether, ethyl acetate, toluene, methylene chloride and the likemay be utilized.

Brominating agents suitable for use in the process of this inventioninclude, but are not limited to, bromine/triphenyl phosphine complexes,phosphorus tribromide, thionyl bromide, concentrated hydrobromic acid,and the like, and mixtures thereof. Bromine/triphenyl phosphinecomplexes are preferred brominating agents.

First solvents suitable for use in the present invention include, butare not limited to, aromatic hydrocarbons such as toluene, benzene,xylenes, mesitylene and the like, halogenated aromatic hydrocarbons suchas chlorobenzene, fluorobenzene and the like, carboxylic acid amidessuch as N,N-dimethyl-formamide and the like, ethers such astetrahydrofuran, dioxane and the like, and halogenated hydrocarbons suchas chloroform, carbon tetrachloride and the like, and mixtures thereof.Preferred first solvents include halogenated hydrocarbons with carbontetrachloride being more preferred.

Second solvents useful in the process of this invention include, but arenot limited to, aromatic hydrocarbons such as toluene, benzene, xylenes,mesitylene and the like, halogenated aromatic hydrocarbons such aschlorobenzene, fluorobenzene and the like, carboxylic acid amides suchas N,N-dimethylformamide and the like, glycols such as dimethoxyethaneand the like, C₁-C₄ alcohols such as methanol, ethanol and the like,ketones such as acetone and the like, and ethers such astetrahydrofuran, dioxane and the like, and mixtures thereof, andmixtures with water. Preferred second solvents include aromatichydrocarbons and aromatic hydrocarbon/C₁-C₄alcohol mixtures with atoluene/ethanol mixture being more preferred.

Palladium catalysts suitable for use in the present invention include,but are not limited to, palladium(O) catalysts such asbis(dibenzylideneacetone)palladium(O),tetrakis(triphenylphosphine)palladium(O) and the like, palladium(II)catalysts such as bis(acetonitrile)-palladium(II) chloride,bis(triphenylphosphine)-palladium(II) chloride,[1,4-bis(diphenylphosphine)-butane]palladium(II) dichloride,[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) diacetate,palladium(II) acetate, palladium(II) chloride and the like, andpalladium on activated carbon, and mixtures thereof. Preferred catalystsinclude palladium(O) catalysts withbis(dibenzylideneacetone)palladium(O) being more preferred.

Bases suitable for use in this invention include, but are not limitedto, alkali metal carbonates such as sodium carbonate and potassiumcarbonate, alkaline earth metal carbonates such as calcium carbonate andthe like, alkali metal hydrogen carbonates such as sodium hydrogencarbonate and the like, alkali metal hydroxides such as sodium hydroxideand potassium hydroxide, alkaline earth metal hydroxides such as calciumhydroxide and the like, alkali metal C₁-C₆alkoxides such as potassiumtertbutoxide and the like, thallium(I) carbonate, thallium(I)C₁-C₆alkoxides, thallium(I) hydroxide, and tri(C₁-C₄alkyl)amines such astrimethylamine, and mixtures thereof. Preferred bases include alkalimetal carbonates with potassium carbonate being more preferred.

In another preferred embodiment of the present invention, a4-aryl-1-bromo-2-fluoro-2-butene of formula III is reacted with apalladium catalyst, a base and a boronic acid of formula IV.

Boronic acids of formula IV, boronic anhydrides of formula V, and borateesters of formula VI may be prepared, as illustrated in Flow Diagram I,by reacting an aryl compound of formula VII with a tri(C₁-C₄alkyl)borate of formula VIII to form the formula VI borate ester, andhydrolyzing the formula VI borate ester with aqueous acid to form theboronic acid of formula IV which may spontaneously combine with otherformula IV compounds to form the boronic anhydride of formula V.

Starting 4-aryl-2-fluoro-2-butene-1-ol compounds of formula II may beprepared according to the procedures described in WO 94/06741 and GB2,288,803-A.

In another preferred embodiment of the present invention, a4-aryl-2-fluoro-2-butene-1-ol of formula II is reacted with abrominating agent in a temperature range of about 50° C. to 130° C., anda 4-aryl-1 bromo-2-fluoro-2-butene of formula III is reacted with apalladium catalyst, a base and a formula IV, V on VI compound in atemperature range of about 50° C. to 130° C.

Preferred formula I fluoroolefin compounds which may be prepared by theprocess of this invention are those wherein

R is hydrogen and R₁ is isopropyl or cyclopropyl, or R and R₁ aremethyl, or R and R₁ are taken together with the carbon atom to whichthey are attached to form a cyclopropyl group;

Ar is phenyl optionally substituted with any combination of from one tothree halogen, C_(l)-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups; and

Ar₁ is 3-phenoxyphenyl optionally substituted with any combination offrom one to five halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups,

3-biphenyl optionally substituted with any combination of from one tofive halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy or C₁-C₄haloalkoxygroups,

3-benzylphenyl optionally substituted with any combination of from oneto five halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups, or

3-benzoylphenyl optionally substituted with any combination of from oneto five halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups.

The process of the present invention is also preferably used for thepreparation of pesticidal fluoroolefins of formula I wherein

R and R₁ are methyl, or R and R₁ are taken together with the carbon atomto which they are attached to form a cyclopropyl group;

Ar is phenyl optionally substituted with any combination of from one tothree halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups; and

Ar₁ is 3-phenoxyphenyl optionally substituted with any combination offrom one to five halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups.

In order to facilitate a further understanding of the invention, thefollowing examples are presented primarily for the purpose ofillustrating more specific details thereof. The scope of the inventionshould not be deemed limited by the examples, but encompasses all thesubject matter defined in the claims.

EXAMPLE 1 Preparation of1-(p-Chlorophenyl)-1-(3-bromo-2-fluoropropenyl)cyclopropane, (Z)—

Under a nitrogen atmosphere, a solution of bromine (0.767 g, 4.8 mmol)in carbon tetrachloride at ice-water bath temperature is treatedsequentially with a solution of triphenylphosphine (1.26 g, 4.8 mmol) incarbon tetrachloride and a solution of3-[1-(p-chlorophenyl)-cyclopropyl]-2-fluoro-2-propen-1-ol, (Z)—(0.907 g,4 mmol) in carbon tetrachloride, heated to and stirred at reflux for 70minutes, cooled to room temperature, and poured into petroleum ether.The resultant mixture is filtered, and the filtrate is concentrated invacuo to obtain a residue. The residue is dissolved in petroleum etherand passed through a plug of silica gel (eluted with hexanes) to obtainan oil. Flash column chromatography of the oil using silica gel and a3:20 methylene chloride/hexanes solution gives the title product as acolorless oil (0.73 g, 63% yield) which is identified by NMR spectralanalyses.

EXAMPLE 2 Preparation of 1-(p-Chlorophenyl)-1-[2-fluoro-3-(4-fluoro-3-phenoxyphenyl)propenyl]cyclopropane, (Z)—

Under a nitrogen atmosphere, a mixture of1-(p-chlorophenyl)-1-(3-bromo-2-fluoropropenyl)cyclopropane, (Z)—(0.434g, 1.5 mmol), 4-fluoro-3-phenoxybenzene-boronic acid (0.452 g, 1.95mmol), potassium carbonate (1.86 g, 13.5 mmol) andbis(dibenzylideneacetone)-palladium(O) (Pd(dba)₂, 4.3 mg, 0.075 mmol) intoluene is heated at 80° C. for one hour, cooled to room temperature,diluted with water, and filtered through diatomaceous earth. The phasesare separated and the aqueous phase is extracted with ethyl acetate. Theorganic phase and ethyl acetate extract are combined, washed with water,dried over anhydrous sodium sulfate and concentrated in vacuo to obtaina residue. Flash column chromatography of the residue using silica geland a 3:20 methylene chloride/hexanes solution gives the title productas an oil (0.274 g, 63% yield) which is identified by NMR spectralanalyses.

As can be seen from the data in Examples 1 and 2,1-(p-chlorophenyl)-1-[2-fluoro-3-(4-fluoro-3-phenoxyphenyl)propenyl]cyclopropane,(Z)—is obtained in 40% yield from3-[1-(p-chlorophenyl)cyclopropyl]-2-fluoro-2-propen-1-ol, (Z)—. Incontrast, WO 94/06741 discloses that1-(p-chlorophenyl)-1-[2-fluoro-3-(4-fluoro-3-phenoxyphenyl)propenyl]cyclopropane,(Z)—is obtained in 20% yield from3-[1-(p-chlorophenyl)cyclopropyl]-2-fluoro-2-propen-1-ol, (Z)—.

EXAMPLE 3 Preparation of1-Bromo-4-(p-chlorophenyl)-2-fluoro-4methyl-2-pentene, (Z)—

Under a nitrogen atmosphere, a solution of triphenyl phosphine (0.96 g,4.25 mmol) in carbon tetrachloride at −5° C. is treated dropwise with asolution of bromine (0.679 g, 4.25 mmol) in carbon tetrachloride, warmedto and stirred at room temperature for 45 minutes, treated with asolution of 4-(p-chlorophenyl)-2-fluoro-4-methyl-2-penten-1-ol,(Z)—(0.81 g, 3.54 mmol) in carbon tetrachloride, refluxed for 2 hours,cooled to room temperature, and poured into petroleum ether. Theresultant mixture is filtered through diatomaceous earth. The filtrateis washed sequentially with water, saturated sodium hydrogen carbonatesolution and brine, dried over anhydrous sodium sulfate and concentratedin vacuo to obtain an oil. Flash column chromatography of the oil usingsilica gel and a 1:9 ethyl acetate/hexanes solution gives the titleproduct as a colorless oil (0.736 g, 71% yield) which is identified byNMR spectral analyses.

EXAMPLE 4 Preparation of4-(p-Chlorophenyl)-2-fluoro-1-(4-fluoro-3-phenoxyphenyl)-4-methyl-2-pentene,(Z)—

Under a nitrogen atmosphere, a mixture of1-bromo-4-(p-chlorophenyl)-2-fluoro-4-methyl-2-pentene, (Z)—(320.8 mg,1.1 mmol), bis(dibenzylideneacetone)palladium(O) (Pd(dba)₂, 31.6 mg,0.055 mmol) in toluene (8 mL) is treated with potassium carbonate (608mg, 4.4 mmol), degassed, treated with a solution of4-fluoro-3-phenoxybenzeneboronic acid (331.8 mg, 1.43 mmol) in ethanol(2 mL), refluxed for 45 minutes, cooled to room temperature, andfiltered through diatomaceous earth. The filtrate is diluted with ethylacetate, and the resultant solution is washed sequentially with waterand brine, dried over anhydrous sodium sulfate, and concentrated invacuo to obtain a residue. Flash column chromatography of the residueusing silica gel and a 1:9 ethyl acetate/hexanes solution gives thetitle product as a colorless liquid (401 mg, 91% yield) which isidentified by NMR spectral analyses.

As can be seen from the data in Examples 3 and 4,4-(p-chlorophenyl)-2-fluoro-1-(4-fluoro-3-phenoxyphenyl)-4-methyl-2-pentene,(Z)—is obtained in 65% yield from4-(p-chlorophenyl)-2-fluoro-4-methyl-2-penten-1-ol, (Z)—. In contrast,GB 2,288,803-A discloses that4-(p-chlorophenyl)-2-fluoro-1-(4-fluoro-3-phenoxyphenyl)-4-methyl-2-pentene,(Z)—is obtained in 37% yield from4-(p-chlorophenyl)-2-fluoro-4-methyl-2-penten-1-ol, (Z)—.

EXAMPLE 5 Preparation of 4-Fluoro-3-phenoxybenzeneboronic acid

A solution of 5-bromo-2-fluorophenyl phenyl ether (8.01 g, 3 mmol) intetrahydrofuran is added dropwise to a mixture of magnesium turnings(0.0802 g, 3.3 mmol), a crystal of iodine and a few drops of1,2-dibromoethane in tetrahydrofuran at 50-55° C. under nitrogen. Afterthe addition is complete, the reaction mixture is stirred at 50-55° C.for 70 minutes and cooled to room temperature. The cooled mixture isadded over 25 minutes to a solution of trimethyl borate (4.09 mL, 3.6mmol) in diethyl ether at dry-ice/acetone bath temperature. After theaddition is complete, the mixture is stirred at dry-ice/acetone bathtemperature for 20 minutes, allowed to warm to −10° C. over 25 minutes,diluted sequentially with acetic acid and water, stirred at roomtemperature for 30 minutes, and extracted with ether. The organicextract is washed with water, dried over anhydrous sodium sulfate, andconcentrated in vacuo to obtain a residue. A mixture of the residue inwater is heated over a steam bath for 30 minutes, cooled to roomtemperature and filtered to obtain a solid which is washed with hexanesand dried to give the title product as a colorless solid (5.7 g, mp177-180° C., 82% yield).

We claim:
 1. A compound having the structural formula

wherein R is hydrogen or C₁-C₄alkyl, or R and R₁ are taken together withthe carbon atom to which they are attached to form a cyclopropyl group;R₁ is C₁-C₄alkyl or cyclopropyl, or R and R₁ are taken together with thecarbon atom to which they are attached to form a cyclopropyl group; Aris phenyl optionally substituted with any combination of from one tothree halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy orC₁-C₄haloalkoxy groups, or 1- or 2-naphthyl optionally substituted withany combination of from one to three halogen, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy or C₁-C₄haloalkoxy groups; and theconfiguration of the groups ArCRR₁—and —CH₂Br about the double bondbeing predominately mutually trans.
 2. The compound according to claim 1selected from the group consisting of1-(p-chlorophenyl)-1-(3-bromo-2-fluoropropenyl)cyclopropane, (Z)—; and1-bromo-4-(p-chlorophenyl)-2-fluoro-4-methyl-2-pentene, (Z)—.
 3. Aprocess for making a compound according to claim 1 which processcomprises reacting a 4-aryl-2-fluoro-2-butene-1-ol compound havingstructural formula

wherein R,R₁and Ar are as defined in claim 1, with a brominating agentselected from the group consisting of a bromine-triphenyl phosphinecomplex, phosphorus tribromide, thionyl bromide, HBr, and mixturesthereof, in a solvent at a temperature of about 50-130° C.